Siddiqi, Tariq Jamal

Background: RCTs studying the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on cardiovascular (CV) risk factors and outcomes have been underpowered to assess patients with overweight or obesity, thus presenting the need for a meta-analysis. Methods: Electronic databases were queried up till February 2022 for RCTs comparing SGLT2i with placebo in patients with overweight (BMI ≥25 kg/m2) or obesity (BMI ≥30 kg/m2) - irrespective of diabetes status - with a follow-up of ≥24 weeks. Meta-analyses were performed using the generic inverse variance technique and a random-effects model. Results are presented as weighted mean differences (WMD) for continuous outcomes, and hazard ratios (HR) for dichotomous outcomes. Outcomes studied were: (i) weight; (ii) systolic BP; (iii) diastolic BP; (iv) heart rate; (v) HDL-C; (vi) LDL-C; (vii) major adverse cardiac events (MACE), i.e., composite of CV death, non-fatal myocardial infarction (MI) and non-fatal stroke; (viii) composite of heart failure hospitalization and CV death (HFH/CV death); (ix) mortality; (x) MI; and (xi) stroke. Results: Seventeen RCTs (47,649 patients) were included. Compared with placebo, SGLT2i significantly reduced weight (WMD: -2.32 kg [-2.77, -1.88]), HbA1c (WMD: -0.79 % [-0.98, - 0.61]) and systolic BP (WMD: -2.15 mm Hg [-3.08, - 1.22]). SGLT2i did not have a significant effect on diastolic BP (WMD: -0.55 mmHg [-1.51, 0.41]), heart rate (WMD: 0.08 bpm. [-0.21, 0.37]), HDL-C (WMD: 1.62 mmol l -1 [-0.21, 3.45]) or LDL-C (WMD: 0.53 mmol l -1 [-0.88, 1.94]). Amongst CV outcomes, SGLT2i reduced the risk of MACE (HR: 0.90 [0.81, 0.99]), HFH/CV death (HR: 0.82 [0.75, 0.90]), and mortality (HR: 0.85 [0.77, 0.94]). No effect was noted on stroke (HR: 0.99 [0.85, 1.26]) or MI (HR: 0.89 [0.77, 1.02]). Conclusions: In patients with overweight or obesity, SGLT2i produce a modest but significant reduction in weight, systolic BP and HbA1c. SGLT2i may also reduce the risk of MACE, HFH/CV death, and mortality.

Abstract Aims There are several risk scores designed to predict mortality in patients with heart failure (HF). This study aimed to assess performance of risk scores validated for mortality prediction in patients with acute HF (AHF) and chronic HF. Methods and results MEDLINE and Scopus were searched from January 2015 to January 2021 for studies which internally or externally validated risk models for predicting all-cause mortality in patients with AHF and chronic HF. Discrimination data were analysed using C-statistics, and pooled using generic inverse-variance random-effects model. Nineteen studies (n = 494 156 patients; AHF: 24 762; chronic HF mid-term mortality: 62 000; chronic HF long-term mortality: 452 097) and 11 risk scores were included. Overall, discrimination of risk scores was good across the three subgroups: AHF mortality [C-statistic: 0.76 (0.68–0.83)], chronic HF mid-term mortality [1 year; C-statistic: 0.74 (0.68–0.79)], and chronic HF long-term mortality [≥2 years; C-statistic: 0.71 (0.69–0.73)]. MEESSI-AHF [C-statistic: 0.81 (0.80–0.83)] and MARKER-HF [C-statistic: 0.85 (0.80–0.89)] had an excellent discrimination for AHF and chronic HF mid-term mortality, respectively, whereas MECKI had good discrimination [C-statistic: 0.78 (0.73–0.83)] for chronic HF long-term mortality relative to other models. Overall, risk scores predicting short-term mortality in patients with AHF did not have evidence of poor calibration (Hosmer–Lemeshow P > 0.05). However, risk models predicting mid-term and long-term mortality in patients with chronic HF varied in calibration performance. Conclusions The majority of recently validated risk scores showed good discrimination for mortality in patients with HF. MEESSI-AHF demonstrated excellent discrimination in patients with AHF, and MARKER-HF and MECKI displayed an excellent discrimination in patients with chronic HF. However, modest reporting of calibration and lack of head-to-head comparisons in same populations warrant future studies.

Abstract Aims Anticoagulants are the mainstay treatment for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), and the CHA2DS2-VASc score is widely used to guide anticoagulation therapy in this cohort. However, utility of CHA2DS2-VASc in NVAF patients is debated, primarily because it is a vascular scoring system, which does not incorporate atrial fibrillation related parameters. Therefore, we conducted a meta-analysis to estimate the discrimination ability of CHA2DS2-VASc in predicting ischaemic stroke overall, and in subgroups of patients with or without NVAF. Methods and results PubMed and Embase databases were searched till June 2020 for published articles that assessed the discrimination ability of CHA2DS2-VASc, as measured by C-statistics, during mid-term (2–5 years) and long-term (>5 years) follow-up. Summary estimates were reported as random effects C-statistics with 95% confidence intervals (CIs). Seventeen articles were included in the analysis. Nine studies (n = 453 747 patients) reported the discrimination ability of CHA2DS2-VASc in NVAF patients, and 10 studies (n = 138 262 patients) in patients without NVAF. During mid-term follow-up, CHA2DS2-VASc predicted stroke with modest discrimination in the overall cohort [0.67 (0.65–0.69)], with similar discrimination ability in patients with NVAF [0.65 (0.63–0.68)] and in those without NVAF [0.69 (0.68–0.71)] (P-interaction = 0.08). Similarly, at long-term follow-up, CHA2DS2-VASc had modest discrimination [0.66 (0.63–0.69)], which was consistent among patients with NVAF [0.63 (0.54–0.71)] and those without NVAF [0.67 (0.64–0.70)] (P-interaction = 0.39). Conclusion This meta-analysis suggests that the discrimination power of the CHA2DS2-VASc score in predicting ischaemic stroke is modest, and is similar in the presence or absence of NVAF. More accurate stroke prediction models are thus needed for the NVAF population.

e13096 Background: Several studies have reported the association between atrial fibrillation (AF) and malignant cancer. Recently, results from a large cohort within the Women’s Health Study showed increased incident risk of breast, colon and lung cancer in patients with AF. Therefore, we performed a systematic review to assess the available evidence and a meta-analysis to define the strength of this association. Methods: MEDLINE, Cochrane and Scopus databases were searched for all prospective studies that reported the association between AF and presence of cancer. The HR for incident risk of common cancers was recorded (Breast, Lung, Colorectal) in patients with and without AF. Lung cancer was excluded because the data required for the analysis was not consistently reported. The DerSimonian-Laird random effects meta-analysis was performed to derive pooled Hazard Ratio (HR) estimates for incident risk of colorectal and breast cancer in patients with AF. Q-test was used to assess between-study heterogeneity; I2 statistic was computed to expresses the percentage of the total observed variability due to study heterogeneity. Results: A total of 390,479 participants in 3 prospective studies were included in the analysis. Mean age of participants was 66.3 ± 6.5 with mean follow up for 12.6 years. Patients with atrial fibrillation had 27% more risk of developing colorectal cancer [HR 1.27 (1.07-1.51) p < 0.005, I2= 73%] and 14% more risk of developing breast cancer [HR 1.14 (1.03-1.26) p = 0.01, I2= 37%] as compared to those without atrial fibrillation. Applying these hazard ratios to age adjusted yearly incidence ratios from 2000-2015, one in 5824 new onset AF cases will develop CRC and one in 7474 new onset AF cases will develop breast cancer. Conclusions: There is small but statistically significant increase in risk of subsequent diagnosis of colorectal or breast cancer diagnosis in patients with AF. Shared risk factors such as old age or systemic disease processes may explain this association. While the results of this analysis raise interesting questions for future search, these results should not be used as basis to initiate cancer screening for an occult cancer in a patient with AF.